Permanent upregulation of hippocampal mineralocorticoid receptors after neonatal administration of ACTH-(4–9) analog ORG 2766 in rats

Abstract

The development of brain corticosteroid receptors may be permanently modified by perinatal hormone treatments, in particular by hormones of the hypothalamic-pituitary-adrenal axis. Changes in binding characteristics of corticosteroid receptors were investigated in rats treated subcutaneously with 1 μg/g body wt of the ACTH-(4–9) analog peptide ORG 2766 once daily at postnatal days 1, 3 and 5. [ 3H]Corticosterone (CORT) binding capacity ( B max) and affinity ( K d) were determined at 1-, 2- and 3-weeks old and adult ages in the hippocampal cytosol by using saturation analysis. Mineralocorticoid type receptor (MR) and glucocorticoid receptor (GR) sites were measured separately with single-point analysis applying a selective glucocorticoid ligand RU 28362 saturating GR. An increase in [ 3H]CORT binding capacity was found during postnatal development which remained permanently high up to adult age. Separate analysis of MR and GR expression indicated that the increment in the number of corticoid receptor sites was due to an increase in number of MRs in both the young and adult rats. It was concluded that neonatal injections of ACTH-(4–9) peptide resulted in a permanent and selective upregulation of hippocampal MRs, which may underlie the previously observed increased vigilance and novelty-induced behavioral reactivity of the peptide-treated adult rats (Felszeghy, K., Sasvári, M. and Nyakas, C., Horm. Behav., 27 (1993) 380–396). © 1997 Elsevier Science B.V. All rights reserved.